Pharmaceutical composition for preventing and treating senile dementia and preparation method thereof

ABSTRACT

The present disclosure relates to a pharmaceutical composition for preventing and treating senile dementia and preparation method thereof. The active ingredients of the pharmaceutical composition are prepared from raw medicinal materials comprising 20-50 parts by weight of Epimedii Folium and 15-55 parts by weight of Poria; or from raw medicinal materials comprising 20-50 parts by weight of Epimedii Folium, 15-55 parts by weight of Poria and 10-55 parts by weight of Acanthopanax, or from raw medicinal materials comprising 20-50 parts by weight of Epimedii Folium, 15-50 parts by weight of Poria, 15-50 parts by weight of Acanthopanax and 6-15 parts by weight of Anemarrhenae Rhizoma.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. Patent Application No.15/319,346, filed on Dec. 15, 2016, now U.S. Pat. No. 10,646,536, whichis a national phase application of International Application No.PCT/CN2015/081950, filed on Jun. 19, 2015. The International Applicationclaims priority to Chinese Patent Application No. 201410280231.2, filedon Jun. 20, 2014. The aforementioned patent applications are herebyincorporated by reference in their entireties.

TECHNICAL FIELD

The present disclosure relates to pharmaceutical fields, and inparticular to a pharmaceutical composition for preventing and treatingsenile dementia and preparation method thereof.

BACKGROUND

With accelerating of stepping into an aging society throughout theworld, various gerontal neurodegenerative diseases, such as mildcognitive impairment, senile dementia and the like, have become majorrisk factors that threaten human health in later life and decrease lifequality of old people, which brings about serious economic burden andheavy psychological pressure to the society and families Senile dementiacan be divided into Alzheimer's disease (AD), vascular dementia, and amixed dementia that the aforementioned two diseases coexist. Seniledementia is a primary degenerative brain disease occurring in or at theearly stage of the geratic period, and is a persistent dysfunction ofhigher-order nervous activities. Clinically, it is manifested asworsening of cognitive and memory functions, progressive deteriorationof daily life ability, as well as various symptoms such asneuropsychiatric symptoms and behavior dysfunction. Senile dementia is adisease with relatively high incidence, and the data of the World HealthOrganization shows that currently there are approximately 20 millionolder people suffering from senile dementia throughout the world, and itwould be expected that by 2020 there will be more than 30 millionpatients suffering from senile dementia throughout the world. Therefore,it is a research emphasis for medical workers of different countriesthroughout the world to develop a drug for improving cognitionimpairment and treating senile dementia, which gains great attentionfrom Chinese and western medical professions.

Currently, drugs used for treating senile dementia mainly include anacetylcholinesterase (AchE) inhibitor, an anti-immune-inflammation drug,a calcium ion antagonist, an antioxidant and the like. Such drugsapproved by the Food and Drug Administration (FDA) (US) includedonepezil, galanthamine, nimodipine, memantine hydrochloride and thelike. These drugs can only temporarily relieve the deterioration ofcognitive functions of the patients, but cannot suspend the progressionof diseases.

Furthermore, some of the aforementioned drugs have adverse effects suchas serious liver and kidney toxicities, and some of the aforementioneddrugs are too expensive to be afforded by the patients and familymembers thereof. Thus, it still needs to develop a new drug with a goodtherapeutic effect, little toxic and side effects and an appropriateprice. Recently, specialists and scholars from China and abroad turntheir attention to traditional Chinese medicines and natural medicines,and attempt to conduct a research on treatment of senile dementia. Themodern traditional Chinese medicine (TCM) believes that, senile dementiais a common gerontal disease characterized by deficiency in origin andexcess in superficiality, wherein the deficiency in origin is mainlycaused by deficiency of the kidney essence, deficiency of marrow sea,and failure of lucid yang to rise; kidney deficiency is the root causeof senile dementia, and malnutrition of internal organs is closelyrelated to the incidence of senile dementia. Therefore senile dementiais often treated by tonifying Kidney and strengthening essence.

As recorded in Encyclopedia of Chinese herbal medicine, Poria haseffects of removing dampness and promoting diuresis, and calming theheart and strengthening the spleen, which can be used to treat edema andoliguria, dizziness and palpitation due to fluid retention, deficiencyof the spleen and lack of appetite, loose stool or diarrhoea, malaise,and palpitation due to fear and insomnia. Acanthopanacis Senticosi Radixet Rhizoma seu Caulis (also known as “Acanthopanax”) has effects ofinvigorating qi and strengthening the spleen, and tonifying kidney andcalming nerves, which is used to treat Yang deficiency of both spleenand kidney, debilitation and hypodynamia, loss of appetite, waist andknee pain, and insomnia and dreaminess. Epimedii Folium (also known as“Epimedium”)has effects of invigorating kidney and strengthening Yang;dispelling wind and eliminating dampness; strengthening muscles andbones, which is mainly used to treat impotence and spermatorrhea,deficient-cold-type infertility, frequent micturition and incontinence,kidney deficiency and cough with asthma, soreness and weakness of waistand knees, rheumatic arthralgia, hemiplegia, and insensitivity of thelimbs. Anemarrhenae Rhizoma has effects of clearing away heat andpurging pathogenic fire, nourishing Yin and moistening dryness, andquenching thirst and relieving restlessness, which may be used to treatwarm febrile diseases; high fever and polydipsia; cough or asthma; coughcaused by dryness; constipation; osteopyrexia and fever; dysphoria andinsomnia; and diabetes and stranguria with turbid discharge.

SUMMARY

The present disclosure in one aspect provides a pharmaceuticalcomposition for treating or preventing senile dementia, the activeingredients of which are prepared from raw medicinal materialscomprising 20-50 parts by weight of Epimedium (i.e. Epimedii Folium) and15-55 parts by weight of Poria.

The present disclosure in another aspect provides a pharmaceuticalcomposition for treating or preventing senile dementia, the activeingredients of which are prepared from raw medicinal materialscomprising 20-50 parts by weight of Epimedium, 15-55 parts by weight ofPoria and 10-55 parts by weight of Acanthopanax, preferably fromtraditional Chinese medicinal materials comprising 20-30 parts by weightof Epimedium, 20-45 parts by weight of Poria and 20-55 parts by weightof Acanthopanax, more preferably from traditional Chinese medicinalmaterials comprising 30 parts by weight of Epimedium, 30 parts by weightof Poria and 35 parts by weight of Acanthopanax.

The present disclosure in a further aspect provides a pharmaceuticalcomposition for treating or preventing senile dementia, the activeingredients of which are prepared from raw medicinal materialscomprising 20-50 parts by weight of Epimedium, 15-50 parts by weight ofPoria, 15-50 parts by weight of Acanthopanax and 6-15 parts by weight ofAnemarrhenae Rhizoma, preferably from traditional Chinese medicinalmaterials comprising 20-30 parts by weight of Epimedium, 20-30 parts byweight of Poria, 25-50 parts by weight of Acanthopanax, and 10-15 partsby weight of Anemarrhenae Rhizoma, more preferably from traditionalChinese medicinal materials comprising 30 parts by weight of Epimedium,30 parts by weight of Poria, 25 parts by weight of Acanthopanax and 15parts by weight of Anemarrhenae Rhizoma.

In the above traditional Chinese medicinal materials, Poria may bereplaced by Poria cum Radix Pini or Polyporus; and Acanthopanax may bereplaced by Acanthopanacis Cortex (Acanthopanax gracilistylus W.W.Smith) or Acanthopanacis Senticosi Folium (Acanthopanax senticosus(Rupr.et Maxim) Harms).

In a still further aspect, the present disclosure provides a process forpreparing said pharmaceutical compositions in which:

said Poria can be processed by the following steps of extracting saidweight parts of Poria with water 2-3 times each for 1-3 hours whereinthe first extraction is carried out with water that is 6-10 times theweight of Poria; and the second and third extractions each are carriedout with water that is 4-8 times the weight of Poria; filtering theresulting extract solution and concentrating it into a dry extract underreduced pressure; preferably said Poria is processed by the followingsteps of extracting said weight parts of Poria with water 3 times eachfor 1 hour wherein the first extraction is carried out with water thatis 8 times the weight of Poria; and the second and third extractionseach are carried out with water that is 6 times the weight of Poria;filtering the resulting extract solution and concentrating it into a dryextract under reduced pressure;

said Epimedium can be processed by the following steps of extractingsaid weight parts of Epimedium with 30-70% ethanol solution 2-3 timeseach for 1-3 hours, wherein the first extraction is carried out with30-70% ethanol solution that is 7-16 times the weight of Epimedium; andthe second and third extractions each are carried out with 30-70%ethanol solution that is 4-12 times the weight of Epimedium; filteringthe resulting extract solution and recovering ethanol under reducedpressure followed by concentrating it into a dry extract; preferablysaid Epimedium is processed by the following steps of extracting saidweight parts of Epimedium with 50% ethanol solution 3 times each for 1hour, wherein the first extraction is carried out with 50% ethanolsolution that is 9 times the weight of Epimedium; the second extractionis carried out with 50% ethanol solution that is 7 times the weight ofEpimedium and the third extraction is carried out with 50% ethanolsolution that is 5 times the weight of Epimedium; filtering theresulting extract solution and recovering ethanol under reduced pressurefollowed by concentrating it into a dry extract;

said Acanthopanax can be processed by the following steps of extractingsaid weight parts of Acanthopanax with water 2-3 times each for 1-3hours wherein the first extraction is carried out with water that is6-10 times the weight of Acanthopanax; and the second and thirdextractions each are carried out with water that is 4-8 times the weightof Acanthopanax; filtering the resulting extract solution andconcentrating it into a dry extract under reduced pressure; preferablysaid Acanthopanax is processed by the following steps of extracting saidweight parts of Acanthopanax with water 3 times each for 1 hour whereinthe first extraction is carried out with water that is 8 times theweight of Acanthopanax; and the second and third extractions each arecarried out with water that is 6 times the weight of Acanthopanax;filtering the resulting extract solution and concentrating it into a dryextract under reduced pressure; and

said Anemarrhenae Rhizoma can be processed by the following steps ofplacing said weight parts of Anemarrhenae Rhizoma into water that is6-10 times the weight of Anemarrhenae Rhizoma, heating the water untilit boils and then decocting Anemarrhenae Rhizoma for 2-4 hours, removingand keeping the supernatant liquid, repeating the above process on theresulting residue again, and then filtering the combined extractsolution followed by concentrating it into a dry extract; preferablysaid Anemarrhenae Rhizoma is processed by the following steps of placingsaid weight parts of Anemarrhenae Rhizoma into water that is 6 times theweight of Anemarrhenae Rhizoma, heating the water until it boils andthen decocting Anemarrhenae Rhizoma for 2 hours, removing and keepingthe supernatant liquid, repeating the extraction process on theresulting residue again, and then filtering the combined extractsolution followed by concentrating it into a dry extract.

In one embodiment of the present disclosure, the pharmaceuticalcomposition comprising Epimedium and Poria is formed by uniformly mixingthe above dried Epimedium extract and above dried Poria extract. In oneembodiment of the present disclosure, the pharmaceutical compositioncomprising Epimedium, Poria and Acanthopanax is formed by uniformlymixing the above dried Epimedium extract, above dried Poria extract andabove dried Acanthopanax extract. In one embodiment of the presentdisclosure, the pharmaceutical composition comprising Epimedium, Poria,Acanthopanax and Anemarrhenae Rhizoma is formed by uniformly mixing theabove dried Epimedium extract, above dried Poria extract, above driedAcanthopanax extract and above dried Anemarrhenae Rhizoma extract.

Moreover, the present disclosure provides a process for preparing saidpharmaceutical compositions comprising Epimedium, Poria andAcanthopanax, which process comprises the following steps:

extracting said weight parts of Poria and said weight parts ofAcanthopanax, separately or in combination, with water 2-3 times eachfor 1-3 hours, wherein the first extraction is carried out with waterthat is 6-10 times by weight; and the second and third extractions eachare carried out with water that is 4-8 times by weight; filtering theresulting extract solution and concentrating it into a dry extract underreduced pressure; preferably extracting a mixture of said weight partsof Poria and said weight parts of Acanthopanax with water 3 times, eachfor 1 hour wherein the first extraction is carried out with water thatis 8 times the weight of the mixture; and the second and thirdextractions each are carried out with water that is 6 times the weightof the mixture; filtering the resulting extract solution andconcentrating it into a dry extract under reduced pressure;

extracting said weight parts of Epimedium with 30-70% ethanol solution2-3 times each for 1-3 hours wherein the first extraction is carried outwith 30-70% ethanol solution that is 7-16 times the weight of Epimedium;and the second and third extractions each are carried out with 30-70%ethanol solution that is 4-12 times the weight of Epimedium; filteringthe resulting extract solution and recovering ethanol under reducedpressure followed by concentrating it into a dry extract; preferablyextracting said weight parts of Epimedium with 50% ethanol solution 3times each for 1 hour wherein the first extraction is carried out with50% ethanol solution that is 9 times the weight of Epimedium; the secondextraction is carried out with 50% ethanol solution that is 7 times theweight of Epimedium and the third extraction is carried out with 50%ethanol solution that is 5 times the weight of Epimedium; filtering theresulting extract solution and recovering ethanol under reduced pressurefollowed by concentrating it into a dry extract; and

uniformly mixing above two resulting extracts .

Furthermore, the present disclosure provides a process for preparingsaid pharmaceutical compositions comprising Epimedium, Poria,Acanthopanax and Anemarrhenae Rhizoma, which process comprises thefollowing steps:

extracting said weight parts of Poria and said weight parts ofAcanthopanax, separately or in combination, with water 2-3 times eachfor 1-3 hours, wherein the first extraction is carried out with waterthat is 6-10 times by weight, and the second and third extractions eachare carried out with water that is 4-8 times by weight; filtering theresulting extract solution and concentrating it into a dry extract underreduced pressure; preferably extracting a mixture of said weight partsof Poria and said weight parts of Acanthopanax with water 3 times, eachfor 1 hour wherein the first extraction is carried out with water thatis 8 times the weight of the mixture; and the second and thirdextractions each are carried out with water that is 6 times the weightof the mixture; filtering the resulting extract solution andconcentrating it into a dry extract under reduced pressure;

extracting said weight parts of Epimedium with 30-70% ethanol solution2-3 times each for 1-3 hours wherein the first extraction is carried outwith 30-70% ethanol solution that is 7-16 times the weight of Epimedium;and the second and third extractions each are carried out with 30-70%ethanol solution that is 4-12 times the weight of Epimedium; filteringthe resulting extract solution and recovering ethanol under reducedpressure followed by concentrating it into a dry extract; preferablyextracting said weight parts of Epimedium with 50% ethanol solution 3times each for 1 hour wherein the first extraction is carried out with50% ethanol solution that is 9 times the weight of Epimedium; the secondextraction is carried out with 50% ethanol solution that is 7 times theweight of Epimedium and the third extraction is carried out with 50%ethanol solution that is 5 times the weight of Epimedium; filtering theresulting extract solution and recovering ethanol under reduced pressurefollowed by concentrating it into a dry extract;

placing said weight parts of Anemarrhenae Rhizoma into water that is6-10 times the weight of Anemarrhenae Rhizoma, heating the water untilit boils and then decocting Anemarrhenae Rhizoma for 2-4 hours, removingand keeping the supernatant liquid, repeating the extraction process onthe resulting residue again, and then filtering the combined extractsolution followed by concentrating it into a dry extract; preferablyplacing said weight parts of Anemarrhenae Rhizoma into water that is 6times the weight of Anemarrhenae Rhizoma, heating the water until itboils and then decocting Anemarrhenae Rhizoma for 2 hours, removing andkeeping the supernatant liquid, repeating the extraction process on theresulting residue again, and then filtering the combined extractsolution followed by concentrating it into a dry extract; and

uniformly mixing above three resulting extracts.

DETAILED DESCRIPTION Example 1. Preparation of PharmaceuticalComposition

A. Extract from Epimedium (Pharmaceutical Composition A)

3 Kg of Epimedium was extracted with 50% ethanol solution 3 times eachfor 1 hour. The first extraction was carried out with 50% ethanolsolution that was 9 times the weight of Epimedium, the second extractionwas carried out with 50% ethanol solution that was 7 times the weight ofEpimedium, and the third extraction was carried out 50% ethanol solutionthat was 5 times the weight of Epimedium. The resulting extract solutionwas filtered and then concentrated into a dry extract under reducedpressure.

B. Extract from Poria (Pharmaceutical Composition B)

3 Kg of Poria was extracted with water 3 times each for 1 hour. Thefirst extraction was carried out with water that was 8 times the weightof Poria, the second and third extractions each were carried out withwater that was 6 times the weight of Poria. The resulting extractsolution was filtered and then concentrated into a dry extract underreduced pressure.

C. Extract from Acanthopanax (Pharmaceutical Composition C)

3 Kg of Acanthopanax was extracted with water 3 times each for 1 hour.The first extraction was carried out with water that was 8 times theweight of Acanthopanax, the second and third extractions each werecarried out with water that was 6 times the weight of Acanthopanax. Theresulting extract solution was filtered and then concentrated into a dryextract under reduced pressure, yielding 0.12 kg.

D. Extract from Anemarrhenae Rhizoma (Pharmaceutical Composition D)

3 Kg of Anemarrhenae Rhizoma was added to water that was 6 times theweight of Anemarrhenae Rhizoma, the water was heated to boiling andAnemarrhenae Rhizoma was decocted for 2 hours. After that, thesupernatant liquid was removed and kept, and the above process wasrepeated on the resulting residue again. The resulting extract solutionswere combined and filtered and then concentrated into a dry extractunder reduced pressure.

Preparation of Pharmaceutical Composition E consisting of 20 parts byweight of Epimendium and 50 parts by weight of Poria

5 Kg of Poria was extracted with water 3 times each for 1 hour. Thefirst extraction was carried out with water that was 8 times the weightof Poria, the second and third extractions each were carried out withwater that was 6 times the weight of Poria. The resulting extractsolution was filtered and then concentrated into a dry extract underreduced pressure. 2 Kg of Epimedium was extracted with 50% ethanolsolution 3 times each for 1 hour. The first extraction was carried outwith 50% ethanol solution that was 9 times the weight of Epimedium, thesecond extraction was carried out with 50% ethanol solution that was 7times the weight of Epimedium, and the third extraction was carried out50% ethanol solution that was 5 times the weight of Epimedium. Theresulting extract solution was filtered and then concentrated into a dryextract under reduced pressure. The above two resulting extracts weremixed uniformly.

Preparation of Pharmaceutical Composition F consisting of 40 parts byweight of Epimendium and 55 parts by weight of Poria

1.1 Kg of Poria was extracted with water 3 times each for 1 hour. Thefirst extraction was carried out with water that was 8 times the weightof Poria, the second and third extractions each were carried out withwater that was 6 times the weight of Poria, respectively. The resultingextract solution was filtered and then concentrated into a dry extractunder reduced pressure. 0.8 Kg of Epimedium was extracted with 50%ethanol solution 3 times each for 1 hour. The first extraction wascarried out with 50% ethanol solution that was 9 times the weight ofEpimedium, the second extraction was carried out with 50% ethanolsolution that was 7 times the weight of Epimedium, and the thirdextraction was carried out 50% ethanol solution that was 5 times theweight of Epimedium. The resulting extract solution was filtered andthen concentrated into a dry extract under reduced pressure. The abovetwo resulting extracts were mixed uniformly.

Preparation of Pharmaceutical Composition F′ consisting of 40 parts byweight of Epimendium and 55 parts by weight of Poria

1.1 Kg of Poria was extracted with water 2 times each for 3 hour. Thefirst extraction was carried out with water that was 6 times the weightof Poria, the second extraction was carried out with water that was 4times the weight of Poria. The resulting extract solution was filteredand then concentrated into a dry extract under reduced pressure. 1 Kg ofEpimedium was extracted with 70% ethanol solution 2 times each for 1hour. The first extraction was carried out with 70% ethanol solutionthat was 7 times the weight of Epimedium and the second extraction wascarried out with 70% ethanol solution that was 4 times the weight ofEpimedium. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. The above tworesulting extracts were mixed uniformly.

Preparation of Pharmaceutical Composition G consisting of 50 parts byweight of Epimendium and 15 parts by weight of Poria

0.3 Kg of Poria was extracted with water 3 times each for 1 hour. Thefirst extraction was carried out with water that was 8 times the weightof Poria, and the second and third extractions each were carried outwith water that was 6 times the weight of Poria. The resulting extractsolution was filtered and then concentrated into a dry extract underreduced pressure. 1 Kg of Epimedium was extracted with 50% ethanolsolution 3 times each for 1 hour. The first extraction was carried outwith 50% ethanol solution that was 9 times the weight of Epimedium, thesecond extraction was carried out with 50% ethanol solution that was 7times the weight of Epimedium, and the third extraction was carried outwith 50% ethanol solution that was 5 times the weight of Epimedium. Theresulting extract solution was filtered and ethanol was recovered underreduced pressure followed by concentrating it into a dry extract. Theabove two resulting extracts were mixed uniformly.

Preparation Of Pharmaceutical Composition G′ consisting of 50 parts byweight of Epimendium and 15 parts by weight of Poria

0.3 Kg of Poria was extracted with water 2 times each for 3 hours. Thefirst extraction was carried out with water that was 10 times the weightof Poria and the second extractions was carried out with water that was8 times the weight of Poria. The resulting extract solution was filteredand then concentrated into a dry extract under reduced pressure. 1 Kg ofEpimedium was extracted with 30% ethanol solution 2 times each for 3hours. The first extraction was carried out with 30% ethanol solutionthat was 16 times the weight of Epimedium and the second extraction wascarried out with 30% ethanol solution that was 12 times the weight ofEpimedium. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure after recoveringethanol. The above two resulting extracts were mixed uniformly.

Preparation of Pharmaceutical Composition H Consisting of 50 Parts byWeight of Epimendium, 15 Parts by Weight of Poria and 10 Parts by Weightof Acanthopanax

1 Kg of Acanthopanax was extracted with water 3 times each for 1 hour.The first extraction was carried out with water that was 8 times theweight of Acanthopanax and the second and third extractions each werecarried out with water that was 6 times the weight of Acanthopanax. Theresulting extract solution was filtered and then concentrated into a dryextract under reduced pressure. 1.5 Kg of Poria was extracted with water3 times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of Poria and the second and thirdextractions each were carried out with water that was 6 times the weightof Poria. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 5 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. The above resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition H′ consisting of 50 parts byweight of Epimendium, 15 parts by weight of Poria and 10 parts by weightof Acanthopanax

1 Kg of Acanthopanax was extracted with water 2 times each for 1 hour.The first extraction was carried out with water that was 6 times theweight of Acanthopanax and the second and third extractions each werecarried out with water that was 4 times the weight of Acanthopanax. Theresulting extract solution was filtered and then concentrated into a dryextract under reduced pressure. 1.5 Kg of Poria was extracted with water2 times each for 3 hours. The first extraction was carried out withwater that was 6 times the weight of Poria and the second extraction wascarried out with water that was 4 times the weight of Poria. Theresulting extract solution was filtered and then concentrated into a dryextract under reduced pressure. 5 Kg of Epimedium was extracted with 70%ethanol solution 2 times each for 1 hour. The first extraction wascarried out with 70% ethanol solution that was 7 times the weight ofEpimedium and the second extraction was carried out with 70% ethanolsolution that was 4 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. The above resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition I consisting of 25 parts byweight of Epimendium, 45 parts by weight of Poria and 25 parts by weightof Acanthopanax

A mixture of 9 kg of Poria and 5 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 5 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. The above resulting two extracts were mixed uniformly.

Preparation of Pharmaceutical Composition J consisting of 30 parts byweight of Epimendium, 30 parts by weight of Poria and 35 parts by weightof Acanthopanax

A mixture of 3 kg of Poria and 3.5 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 3 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. The above resulting two extracts were mixed uniformly.

Preparation of Pharmaceutical Composition K consisting of 20 parts byweight of Epimendium, 40 parts by weight of Poria and 55 parts by weightof Acanthopanax

A mixture of 0.8 kg of Poria and 1.1 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 0.4 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. The above resulting two extracts were mixed uniformly.

Preparation of Pharmaceutical Composition L consisting of 20 parts byweight of Epimendium, 55 parts by weight of Poria and 20 parts by weightof Acanthopanax

A mixture of 1.1 kg of Poria and 0.4 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 0.4 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. The above resulting two extracts were mixed uniformly.

Preparation of Pharmaceutical Composition L′ consisting of 20 parts byweight of Epimendium, 55 parts by weight of Poria and 20 parts by weightof Acanthopanax

A mixture of 1.1 kg of Poria and 0.4 kg of Acanthopanax was extracted 2times each for 3 hours. The first extraction was carried out with waterthat was 10 times the weight of the mixture and the second extractionwas carried out with water that was 8 times the weight of the mixture.The resulting extract solution was filtered and then concentrated into adry extract under reduced pressure. 0.4 kg of Epimedium was extractedwith 30% ethanol solution 2 times each for 3 hours. The first extractionwas carried out with 30% ethanol solution that was 16 times the weightof Epimedium, the second and third extractions each were carried outwith 30% ethanol solution that was 12 times the weight of Epimedium. Theresulting extract solution was filtered, ethanol was recovered from thesolution under reduced pressure and then the solution was concentratedinto a dry extract. The above resulting two extracts were mixeduniformly.

Preparation of Pharmaceutical Composition M consisting of 50 parts byweight of Epimendium, 15 parts by weight of Poria, 15 parts by weight ofAcanthopanax and 15 parts by weight of Anemarrhenae Rhizoma

A mixture of 3 kg of Poria and 3 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 10 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium, and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. 3 Kg of Anemarrhenae Rhizoma was added to water that was 6times the weight of Anemarrhenae Rhizoma, the water was heated toboiling and Anemarrhenae Rhizoma was decocted for 2 hours. After thatthe supernatant liquid was removed and kept, and the above process wasrepeated on the resulting residue again. Then the combined extractsolution was filtered and concentrated into a dry extract under reducedpressure. The above resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition M′ consisting of 50 parts byweight of Epimendium, 15 parts by weight of Poria, 15 parts by weight ofAcanthopanax and 15 parts by weight of Anemarrhenae Rhizoma

A mixture of said parts by weight of Poria and said parts by weight ofAcanthopanax was extracted 3 times each for 1 hour. The first extractionwas carried out with water that was 6 times the weight of the mixtureand the second and third extractions each were carried out with waterthat was 4 times the weight of the mixture. The resulting extractsolution was filtered and then concentrated into a dry extract underreduced pressure. Epimedium in above parts by weight was extracted with30% ethanol solution 3 times each for 3 hours. The first extraction wascarried out with 30% ethanol solution that was 16 times the weight ofEpimedium, the second and third extractions each were carried out with30% ethanol solution that was 12 times the weight of Epimedium. Theresulting extract solution was filtered, ethanol was recovered from thesolution under reduced pressure and then the solution was concentratedinto a dry extract. Anemarrhenae Rhizoma in said parts by weight wasadded to water that was 6 times the weight of Anemarrhenae Rhizoma, thewater was heated to boiling and Anemarrhenae Rhizoma was decocted for 2hours. After that the supernatant was taken, the above process wasrepeated on the resulting residue again. Then the combined extractsolution was filtered and concentrated into a dry extract under reducedpressure. The above resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition N consisting of 25 parts byweight of Epimendium, 30 parts by weight of Poria, 30 parts by weight ofAcanthopanax and 10 parts by weight of Anemarrhenae Rhizoma

A mixture of 6 kg of Poria and 6 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 5 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium, and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. 2 Kg of Anemarrhenae Rhizoma was added to water that was 6times the weight of Anemarrhenae Rhizoma, the water was heated toboiling and Anemarrhenae Rhizoma was decocted for 2 hours. After thatthe supernatant was removed and kept, and the above process was repeatedon the resulting residue again. Then the combined extract solution wasfiltered and concentrated into a dry extract under reduced pressure. Theabove resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition 0 consisting of 30 parts byweight of Epimendium, 30 parts by weight of Poria, 25 parts by weight ofAcanthopanax and 15 parts by weight of Anemarrhenae Rhizoma

A mixture of 6 kg of Poria and 5 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 6 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium, and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. 3 Kg of Anemarrhenae Rhizoma was added to water that was 6times the weight of Anemarrhenae Rhizoma, the water was heated toboiling and Anemarrhenae Rhizoma was decocted for 2 hours. After thatthe supernatant was removed and kept, and the above process was repeatedon the resulting residue again. Then the combined extract solution wasfiltered and concentrated into a dry extract under reduced pressure. Theabove resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition P consisting of 20 parts byweight of Epimendium, 20 parts by weight of Poria, 50 parts by weight ofAcanthopanax and 12 parts by weight of Anemarrhenae Rhizoma

A mixture of 2 kg of Poria and 5 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 2 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium, and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. 1.2 Kg of Anemarrhenae Rhizoma was added to water that was 6times the weight of Anemarrhenae Rhizoma, the water was heated toboiling and Anemarrhenae Rhizoma was decocted for 2 hours. After thatthe supernatant was removed and kept, and the above process was repeatedon the resulting residue again. Then the combined extract solution wasfiltered and concentrated into a dry extract under reduced pressure. Theabove resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition Q consisting of 20 parts byweight of Epimendium, 50 parts by weight of Poria, 24 parts by weight ofAcanthopanax and 6 parts by weight of Anemarrhenae Rhizoma

A mixture of 5 kg of Poria and 2.4 kg of Acanthopanax was extracted 3times each for 1 hour. The first extraction was carried out with waterthat was 8 times the weight of the mixture and the second and thirdextractions each were carried out with water that was 6 times the weightof the mixture. The resulting extract solution was filtered and thenconcentrated into a dry extract under reduced pressure. 2.0 Kg ofEpimedium was extracted with 50% ethanol solution 3 times each for 1hour. The first extraction was carried out with 50% ethanol solutionthat was 9 times the weight of Epimedium, the second extraction wascarried out with 50% ethanol solution that was 7 times the weight ofEpimedium, and the third extraction was carried out with 50% ethanolsolution that was 5 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. 0.6 Kg of Anemarrhenae Rhizoma was added to water that was 6times the weight of Anemarrhenae Rhizoma, the water was heated toboiling and Anemarrhenae Rhizoma was decocted for 2 hours. After thatthe supernatant was removed and kept, and the above process was repeatedon the resulting residue again. Then the combined extract solution wasfiltered and concentrated into a dry extract under reduced pressure. Theabove resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition Q′ consisting of 20 parts byweight of Epimendium, 50 parts by weight of Poria, 24 parts by weight ofAcanthopanax and 6 parts by weight of Anemarrhenae Rhizoma

A mixture of 5 kg of Poria and 2.4 kg of Acanthopanax was extracted 2times each for 3 hours. The first extraction was carried out with waterthat was 10 times the weight of the mixture and the second extractionwas carried out with water that was 8 times the weight of the mixture.The resulting extract solution was filtered and then concentrated into adry extract under reduced pressure. 2.0 Kg of Epimedium was extractedwith 70% ethanol solution 2 times each for 1 hour. The first extractionwas carried out with 70% ethanol solution that was 7 times the weight ofEpimedium and the second extraction was carried out with 70% ethanolsolution that was 4 times the weight of Epimedium. The resulting extractsolution was filtered, ethanol was recovered from the solution underreduced pressure and then the solution was concentrated into a dryextract. 0.6 Kg of Anemarrhenae Rhizoma was added to water that was 10times the weight of Anemarrhenae Rhizoma, the water was heated toboiling and Anemarrhenae Rhizoma was decocted for 4 hours. After thatthe supernatant was removed and kept, and the above process was repeatedon the resulting residue again. Then the combined extract solution wasfiltered and concentrated into a dry extract under reduced pressure. Theabove resulting three extracts were mixed uniformly.

Preparation of Pharmaceutical Composition R

The preparation process was the same as that of PharmaceuticalComposition J with the exception that Poria was replaced by Poria cumRadix Pini.

Preparation of Pharmaceutical Composition S

The preparation process was the same as that of PharmaceuticalComposition J with the exception that Poria was replaced by Polyporus.

Preparation of Pharmaceutical Composition T

The preparation process was the same as that of PharmaceuticalComposition J with the exception that Acanthopanax was replaced byAcanthopanacis Cortex.

Preparation of Pharmaceutical Composition U

The preparation process was the same as that of PharmaceuticalComposition J with the exception that Acanthopanax was replaced byAcanthopanacis Senticosi Folium.

As stated above, the present disclosure provides a pharmaceuticalcomposition with a simple formulation, which may be used for treating orpreventing senile dementia with definite curative effects.

Example 2. Effect On Learning and Memory in Rats UsingScopolamine-Induced Model

1. Materials

Materials: Morris water maze device available from Tai Meng TechnologyCo. LTD, Chengdu City, China, DT-200 jump platform available from TaiMeng Technology Co. LTD, Chengdu City, China, Scopolamine Hydrobromideinjection (Scop) available from Hua Yida Medical Technology Co. LTD,Wuhan City, China, and Donepezil Hydrochloride available from EisaiChina Inc., China, specification: 5 mg, batch No. 120829A were used.Animals: SD Male rats, available from Da Shuo Biological Technology Co.LTD, Chengdu City, China, were used.2. Testing Method

Animal Grouping and Administration

Rats were randomly divided into Normal control group, Scop Model group,Positive control group (Donepezil, 1.17 mg/kg) and Experimental group(administered with a pharmaceutical composition of Example 1 in anamount of 11.08g raw medicinal materials per kg body weight). Beforeexperiments, rats were fed by intragastric administration for 2 weeks.The normal control group and the model group were fed the same volume ofdistilled water. On day 9, rats were trained in the pool of Morris 2times per day. On day 14, rats were subjected to do Morris water Mazeand jump platform testing.

Model establishment and learning and memory test

On experiment day, rats were intragastrically administered. 30 Minuteslater, they were administered with scopolamine hydrobromide (HBr) byintraperitoneal injections (2 mg·kg⁻¹ for two days and then 1 mg·kg⁻¹ onday 3). 20 Minutes later, rats were subjected to Morris water Mazetesting. The normal control group was intraperitoneally injected withthe same volume of saline. Their swimming performance was tracked andrecorded by a camera. The travel path, time spent and speed of movementof rats in 90 s were recorded by a computer automatically, and theswimming distance and escape latency for finding the platform werecalculated. Jump platform experiment: rats were trained on day one, andsubjected to testing on day 2. 20 Minutes before testing, rats wereintraperitoneally injected with scopolamine HBr in 5 mg·kg⁻¹. The firststep down latency (SDL) and escape latency (the time required to escapefrom electric shock, EL) of rats were recorded.

3. Results

Effect on Morris water Maze tests of rats using Scopolamine inducedDysmnesia Model

TABLE 1 Effect on Morris water maze test (x ± s) Number of animalsGroups (n) Escape latency(s) Distance (cm) Normal control 10 18.86 ±6.03** 540.46 ± 100.24** Model control 10 49.63 ± 9.15 2173.42 ± 388.11Positive control 10 37.27 ± 9.46** 1647.50 ± 286.35** Composition A 1041.69 ± 9.13 1897.60 ± 337.12 Composition B 10 41.42 ± 10.80 1896.44 ±298.22 Composition C 10 42.82 ± 10.06 1875.75 ± 272.57 Composition D 1042.27 ± 8.60 1868.96 ± 293.34 Composition E 10 40.65 ± 8.87* 1794.70 ±333.61* Composition F 10 40.51 ± 8.62* 1826.32 ± 251.11* Composition G10 40.10 ± 8.71* 1792.36 ± 279.36* Composition J 10 35.23 ± 8.20**1644.08 ± 342.53** Composition O 10 34.66 ± 10.37** 1641.50 ± 226.13**Compared with the model control group, *P < 0.05 and **P < 0.01.

The data in Table 1 clearly demonstrate that in the Morris water mazetest, the performance of Scop induced dysmnesia model rats were improvedby using pharmaceutical compositions A, B, C and D although not obvious(P>0.05). Different improvements were achieved when using all otherpharmaceutical compositions, in which the use of composition J andcomposition O produced the most obvious improvement, and the differencewas statistically significant (P<0.01).

Effect on rats jump platform test using Scopolamine induced DysmnesiaModel

TABLE 2 Effect on rats in jump platform test (x ± s) Number of animalsGroups (n) SDL(s) EL(s) Normal control 10 100.60 ± 14.26** 59.41 ±11.80** Model control 10 16.04 ± 7.22 130.63 ± 19.46 Positive control 1028.67 ± 11.70** 109.17 ± 11.17** Composition A 10 22.23 ± 7.69 116.13 ±15.71 Composition B 10 20.85 ± 7.00 115.96 ± 13.43 Composition C 1021.93 ± 6.72 119.95 ± 12.52 Composition D 10 22.76 ± 7.60 119.81 ± 13.66Composition E 10 24.09 ± 5.97* 113.70 ± 13.00* Composition F 10 24.61 ±7.37* 113.50 ± 12.59* Composition G 10 24.26 ± 6.94* 113.52 ± 11.72*Composition J 10 27.71 ± 6.04** 108.98 ± 13.41** Composition O 10 27.83± 5.67** 108.67 ± 12.50** Compared with the model control group, *P <0.05 and **P < 0.01.

The data in Table 2 clearly demonstrate that in the rats jump platformtest, the performance of Scop induced dysmnesia model rats were improvedby using pharmaceutical compositions A, B, C and D although not obvious(P>0.05). Different improvements were achieved when using all otherpharmaceutical compositions, in which composition J and composition Oproduced the most obvious improvement, and the difference wasstatistically significant (P<0.01).

Example 3. Effect on Learning and memory of APPswe Transgenic Mice

1. Materials

Material: Morris water maze device available from Tai Meng TechnologyCo. LTD, Chengdu City, China, Home-made Object Recognition device; andDonepezil Hydrochloride available from Eisai China Inc., Specification:5 mg, batch number 120829A, were used.

Animals: APPswe transgenic mice in 5 months, available from Nanjinganimal model institute, were used.

2. Testing Method

Animal grouping and Administration

APPswe transgenic mice, half male and half female, were randomly dividedinto four groups: model control group, positive control group(donepezil, 1.67 mg-kg⁻), experimental group (administered with apharmaceutical composition of Example 1 in an amount of 15.83 g rawmedicinal materials per kg body weight). APPswe mice with the samebackground and age (available from Nanjing animal model institute,without expression of human presenilin and amyloid precursor protein,and without suffering senile dementia) were used as the normal controlgroup. Each group was given the corresponding drugs by intragastricadministration and the normal control group and model control group weregiven distilled water of the same volume, once a day for 30 days.

Morris water Maze test

On day 25 to day 29 after administration, mice in each group weretrained for water maze, 2 times per day. 1 Hour after the lastadministration, the location of the platform remained unchanged and theescape latency and swimming path of the mice for finding the platformwere recorded by an automatic camera system, in which the maximumlatency time was set as 120 s. The recording automatically stopped after120 s.

Object recognition test

In light of animal's habit of “loving the new and loathing the old” , ahomemade object recognition device was used for detection of animallearning and memory ability. The first day is the adaptation phase,during which mice were put in carton with good lighting and allowed toadapt to it and freely move for about 10 min. The second day is thefamiliar phase, during which two same toys were put in a box and micewere placed in the box for 10 min Exploration time to each object wasrecorded. The third day is the recognition phase, during which anotherobject was placed in the box to replace one toy and exploration time toeach object was recorded. The resolution index to the new toy in eachgroup was calculated according to the following formula:

Resolution index=(the time to the new object−the time to the oldobject)/(the time to the new object+the time to the old object).

3. Results

1) Effect on APPswe mice water Maze test

TABLE 3 Effect on Morris water maze test (x ± s) Number of animalsGroups (n) Escape latency(s) Distance (cm) Normal control 10 50.50 ±9.42** 479.24 ± 94.26** Model control 10 86.14 ± 14.30 982.81 ± 160.96Positive control 10 68.23 ± 12.00** 783.50 ± 145.12** Composition A 1073.07 ± 14.43 840.02 ± 152.86 Composition B 10 74.16 ± 13.58 847.45 ±157.24 Composition C 10 74.70 ± 10.82 842.36 ± 149.22 Composition D 1074.01 ± 12.56 843.20 ± 148.06 Composition H 10 69.54 ± 13.39* 790.90 ±146.33* Composition I 10 66.70 ± 14.48** 759.20 ± 162.61** Composition J10 64.16 ± 13.16** 751.08 ± 175.17** Composition K 10 65.08 ± 12.40**755.08 ± 146.47** Composition L 10 68.93 ± 16.66* 792.65 ± 192.96*Composition R 10 68.50 ± 15.32* 786.33 ± 154.35* Composition S 10 68.87± 14.35* 795.12 ± 142.72* Composition T 10 68.92 ± 13.03* 786.96 ±164.43* Composition U 10 69.34 ± 12.34* 803.46 ± 172.33* Composition M10 67.58 ± 15.21* 776.10 ± 183.60* Composition N 10 63.98 ± 11.06**744.57 ± 157.55** Composition O 10 61.56 ± 15.11** 736.28 ± 149.50**Composition P 10 62.26 ± 11.83** 747.78 ± 144.17** Composition Q 1068.77 ± 13.66* 782.94 ± 156.02* Compared with the model control group,*P < 0.05 and **P < 0.01.

The data in Table 3 clearly demonstrate that in the Morris water Mazetest, the performance of Appswe mice were improved by usingpharmaceutical compositions A, B, C and D although not obvious (P>0.05).Different improvements were achieved when using all other pharmaceuticalcompositions, and compared with the model control group, the differencewas statistically significant (P<0.01-0.15).

2) Effect on APPswe mice object recognition test

TABLE 4 Effect on object recognition test (x ± s) Number of animalsGroups (n) Resolution index Normal control 10 0.304 ± 0.131** Modelcontrol 10 0.105 ± 0.044 Positive control 10 0.176 ± 0.051** CompositionA 10 0.147 ± 0.053 Composition B 10 0.146 ± 0.061 Composition C 10 0.152± 0.058 Composition D 10 0.147 ± 0.049 Composition H 10 0.174 ± 0.074*Composition I 10 0.188 ± 0.064** Composition J 10 0.197 ± 0.078**Composition K 10 0.184 ± 0.055** Composition L 10 0.175 ± 0.067*Composition R 10 0.169 ± 0.074* Composition S 10 0.166 ± 0.056*Composition T 10 0.168 ± 0.072* Composition U 10 0.168 ± 0.080*Composition M 10 0.175 ± 0.075* Composition N 10 0.196 ± 0.045**Composition O 10 0.201 ± 0.055** Composition P 10 0.197 ± 0.062**Composition Q 10 0.174 ± 0.079* Compared with the model control group,*P < 0.05 and **P < 0.01.

The data in Table 4 clearly demonstrate that the exploration time ofAppswe mice was improved by using pharmaceutical compositions A, B, Cand D although not obvious (P>0.05). Different improvements onexploration time of Appswe mice were achieved when using all otherpharmaceutical compositions, and compared with model control group, thedifference was statistically significant (P<0.01˜0.15).

Example 4. Effect on Learning and Memory in Mice UsingScopolamine-Induced Model

1. Materials

Materials: Morris water maze device available from Tai Meng TechnologyCo. LTD, Chengdu City, China, DT-200 jump platform available from TaiMeng Technology Co. LTD, Chengdu City, China, scopolamine HBr injection(Scop) available from Hua Yida Medical Technology Co. LTD, Wuhan City,China, and Donepezil Hydrochloride available from Eisai China Inc.,China, specification: 5 mg, batch No. 120829A were used.

Animals: KM mice, available from Da Shuo Biological Technology Co. LTD,Chengdu City, China, were used.

2. Testing method

Animal Grouping and Administration

Mice were randomly divided into Normal control group, Scop Model group,Positive control group (Donepezil, 1.67 mg/kg) and Experimental group(administered with a pharmaceutical composition of Example 1, in adosage of 31.66 g raw medicinal materials/kg for composition A, B and C,and in a high dosage of 31.66 g raw medicinal materials/kg, a middledosage of 15.83 g raw medicinal materials/kg and a low dosage of 7.92 graw medicinal materials/kg for composition J). Before experiments, miceof experimental group were fed by intragastric administration of apharmaceutical composition for 2 weeks, while the normal control groupand the model group were fed the same volume of distilled water. On day9, mice were trained in the pool of Morris, 2 times per day. On day 14,mice were subjected to Morris water Maze testing.

Model establishment and learning and memory test

On experiment day, mice were fed by intragastric administration. 30Minutes later, they were administered with Scop in a dosage of 3 mg·kg⁻¹via intraperitoneal injection. 20 Minutes later, the mice were subjectedto Morris water Maze testing. The normal control group wasintraperitoneally injected with the same volume of saline. The swimmingperformance of mice were tracked and recorded by a camera. The travelpath, time spent and speed of movement of mice in 300 s were recorded bya computer automatically. The maximum latency was set as 300 s. Therecording stopped after 300 s. The escape latency and swimming distancefor looking for the platform were recorded.

3. Results

TABLE 5 Effect on Mice in Morris water Maze test (x ± s) Number ofSwimming animals Distance Groups (n) Escape latency(s) (cm) Normalcontrol 10 92.09 ± 10.74** 2052.09 ± 232.41** Model control 10 176.54 ±18.74 3646.54 ± 574.35 Positive control 10 141.42 ± 25.85** 2738.70 ±534.75** Composition A 10 154.88 ± 28.38 2920.88 ± 601.84* Composition B10 157.59 ± 25.91 3104.59 ± 396.84* Composition C 10 154.28 ± 22.05*3148.28 ± 589.34 Composition J 10 133.55 ± 28.98** 2453.55 ± 511.18**(high dosage) Composition J 10 136.95 ± 28.74** 2576.95 ± 527.11**(middle dosage) Composition J 10 149.26 ± 24.82* 2989.66 ± 530.04* (lowdosage) Compared with the model control group, *P < 0.05 and **P < 0.01.

The data in Table 5 clearly demonstrate that in the Morris water mazetest, various compositions produced different improvements on theperformance of Scop induced dysmnesia model mice, in which composition Jin the high, middle and low dosage produced the most obviousimprovement, and the difference was significant statistically (P<0.010.05).

Example 5. Clinical Trial Study

1. Selection of subjects:

1.1 Diagnostic Criteria:

The criteria of NINCDS-ADRDA-R were used, including core diagnosticcriteria A, supportive features B and exclusion criteria as shown below.

TABLE 6 Core diagnostic criteria, supportive features and exclusioncriteria Core diagnostic criteria A. Presence of an early andsignificant episodic memory impairment that includes the followingfeatures: 1. Gradual and progressive change in memory function reportedby patients or informants over more than 6 months 2. Objective evidenceof significantly impaired episodic memory on testing: this generallyconsists of recall deficit that does not improve significantly or doesnot normalise with clue or recognition testing and after effectiveencoding of previously control information 3. The episodic memoryimpairment can be isolated or associated with other cognitive changes atthe onset of AD or as AD advances Supportive features B. Presence ofmedial temporal lobe atrophy (MTA) Volume loss of hippocampi, entorhinalcortex, amygdala evidenced on MRI with qualitative ratings using visualscoring (referenced to well characterized population with age norms) orquantitative volumetry of regions of interest (referenced to wellcharacterized population with age norms) C. Abnormal cerebrospinal fluidbiomarker Low amyloid β₁₋₄₂ concentrations, increased total tauconcentrations, or increased phospho-tau concentrations, or combinationsof the three Other well validated markers to be discovered in the futureD. Specific pattern on functional neuroimaging with PET Reduced glucosemetabolism in bilateral temporal parietal regions Other well validatedligands, including those that foreseeably will emerge such as Pittsburgcompound B or FDDNP E. Proven AD autosomal dominant mutation within theimmediate family Exclusion criteria History Sudden onset Earlyoccurrence of the following symptoms: gait disturbances, seizures,behavioural changes Clinical features Focal neurological featuresincluding hemiparesis. sensory loss, visual field deficits Earlyextrapyramidal signs Other medical disorders severe enough to accountfor memory and related symptoms Non-AD dementia Major depressionCerebrovascular disease Toxic and metabolic abnormalities, all of whichmay require specific investigations MRI FLAIR or T2 signal abnormalitiesin the medial temporal lobe that are consistent with infectious orvascular insults1.2. Inclusion Criteria

(1) 60 Years of age or older, male or female.

(2) Meeting the diagnostic criteria of AD, and also meeting the abovecriteria of TCM syndromes.

(3) Degree of education above the primary school.

(4) Without stroke history.

(5) Hachiski ischemic score (HIS) of below 4 points.

(6) Clear and definite Brain MR (with brain atrophy and without othercranial lesions).

(7) MMSE score: 9˜24 scores for middle school or higher; and9˜20 scoresfor primary school; CDR score: mild to moderate patients with 1 or 2scores.

(8) Patients who have not taken any medicines for treating dementia formore than 1 week.

1.3 Exclusion criteria:

(1) Patients who are subjected to severe cardiac or cerebral vasculardiseases, severe liver or kidney disease, or pulmonary infection.

(2) Patients who can't cooperate with the treatment or are subjected todrug allergy.

(3) Patients who are subjected to severe depression (as demonstrated bydepression table).

(4) Patients who are subjected to vascular dementia (VD), Parkinsondisease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporaldementia (FTD) or the like.

(5) Severe AD patients or patients who are subjected to severeneurological impairment so that inspection cannot be completed.

(6) Patients who are taking Aricept, Memantine, Huperzine A,Nimoldipine, Ginseng, Ginkgo folium, saffron or the like currently orwithin 1 week.

1.4 Removal or failure criteria:

(1) Patients who have poor medication compliance or fail to takemedicine for more than 1 month.

(2) Patients who are subjected to serious diseases and have to stay inhospital.

(3) Patients who do not meet the inclusion criteria but have beenmistakenly included or who meet the inclusion criteria but have failedto comply with the prescribed medication.

1.5 Termination criteria:

(1) Patients who suffer other severe disease in the course of the trial.

(2) Patients with serious adverse events during the trial or patientswhose treatments have to stop according to the doctor's judgment.

(3) Patients who cannot continue to be treated due to non-therapeuticreasons or drop out voluntarily.

2. Preparation and administration of trial medicines

350 Kg of Acanthopanax, 300kg of Epimedium and 300 kg of Poria wereextracted as above, thereby affording 26 kg of extract from Acathopanaxand Poria and 54 kg of extract from Epimedium. The obtained extractswere pulverized, added with a proper amount of starch and dextrin, andthen made into granules. After sterilization, the medicament waspackaged in 8 g/bag. The medicament was administered in a dosage of onebag twice per day, morning and evening. The daily dosage of rawmedicinal materials for adults was 30 g of Epimedium, 35 g ofAcanthopanax and 30 g of Poria. The treatment cycle was 6 months.

3. Observation

The following observations were made on patients before enrollment andduring the 6 months of treatment:

(1) ADAS-cog scale.

(2) MMSE scale.

(3) Activities of daily living scale (ADL).

(4) Clinical dementia rating scale (CDR).

(5) Neuropsychiatric Inventory scale (NPI).

4. Standard for evaluation of curative effect

Main index

(1) Cognitive function assessment: comparison of MMSE, ADAS-cog, and CDRscores with baseline levels.

(2) Overall situation: CDR overall assessment.

Secondary index

(1) Assessment of activities of daily living activities: change of ADLscores before and after treatment.

(2) Evaluation of mental behavior: comparative analysis on change of theneuropsychiatric inventory scale (NPI) scores before and aftertreatment.

5. Study results

TABLE 7 Part of the clinical data Before administration After 6 months'administration No. Gender Age MMSE ADAS-cog ADL NPI CDR MMSE ADAS-cogADL NPI CDR 1 M 78 20 29 28 1 1 21 25 20 0 0.5 2 F 80 12 36 31 5 1 17 3022 0 1 3 F 76 20 38 39 3 1 19 27 24 0 1 4 M 73 19 22 26 0 1 27 13 20 00.5 5 M 80 9 45 27 6 2 11 41 31 7 2 6 F 73 13 49 37 0 2 20 41 33 0 2 7 M81 14 38 42 5 2 24 26 38 1 1 8 M 74 21 26 24 0 1 27 17 20 0 0.5 9 F 7412 54 40 11 2 13 38 30 0 1 10 F 76 15 37 24 0 1 21 24 24 0 1 11 F 64 2324 24 0 1 28 15 20 0 0.5 12 F 79 19 32 27 0 1 26 18 23 0 0.5 13 F 78 1055 33 3 2 17 35 27 0 1 14 M 77 13 45 41 2 2 18 35 29 1 1 15 F 84 13 4336 2 2 17 39 32 0 1 16 F 72 21 26 27 2 1 25 15 20 0 0.5

The above clinical data of table 7 were statistically analyzed and theresults were as follows:

TABLE 8-1 Effect on MMSE, ADAS-cog and CDR scores (x ± s, n = 16) MMSEADAS-cog CDR Before After Before After Before After Group administrationadministration administration administration administrationadministration Experimental 15.88 ± 4.46 20.69 ± 5.13** 37.44 ± 10.4827.44 ± 9.90** 1.44 ± 0.51 0.94 ± 0.48** group Compared with thecorresponding values before administration, **P < 0.01

TABLE 8-2 Rating of severity of disease based on CDR scores Number ofimproved cases (improvement rate) CDR scores Before administration After6 months' administration Moderate 7 patients 5 (71.4%) Mild 9 patients 6(66.7%)

The data in Table 8-1 demonstrate that the medication treatment for 6months significantly improved MMSE, ADAS cog and CDR scores, and ascompared with the baseline scores before administration, the differenceswere statistical significant (P<0.01), indicating that the medicamentsignificantly improved cognitive function in AD patients. The data inTable 8-2 demonstrate that, according to the CDR scores, 5 of 7 patientsof moderate AD after taking medicine for 6 months turned to mild,showing an improvement rate of 71.4% and 6 of 9 patients of mild ADafter taking medicine for 6 months turned to suspected dementia, showingan improvement rate of 66.7%.

TABLE 9 Effect on NPI and ADL scores NPI ADL Before After Before AfterGroup administration administration administration administrationExperi- 2.50 ± 3.03 0.56 ± 1.75* 31.62 ± 6.60 25.81 ± 5.73** mentalgroup Compared with the corresponding values before administration, *P <0.05, **P < 0.01

The data in Table 9 clearly demonstrate that patients after takingmedicines for 6 months had obviously improved NPI and ADL, and comparedwith the baseline scores before administration, the differences werestatistically significant (P <0.01-0.05), indicating that the medicamentsignificantly improved nerve and mental conditions and daily lifeability of AD patients.

For the sake of brevity, only certain ranges are explicitly disclosedherein. However, ranges from any lower limit may be combined with anyupper limit to recite a range not explicitly recited, as well as, rangesfrom any lower limit may be combined with any other lower limit torecite a range not explicitly recited, in the same way, ranges from anyupper limit may be combined with any other upper limit to recite a rangenot explicitly recited. Additionally, within a range includes everypoint or individual value between its end points even though notexplicitly recited. Thus, every point or individual value may serve asits own lower or upper limit combined with any other point or individualvalue or any other lower or upper limit, to recite a range notexplicitly recited.

The terms “preferred” and “preferably” refer to embodiments of theinvention that may afford certain benefits, under certain circumstances.However, other embodiments may also be preferred, under the same orother circumstances. Furthermore, the recitation of one or morepreferred embodiments does not imply that other embodiments are notuseful, and is not intended to exclude other embodiments from the scopeof the invention.

Also herein, the recitations of numerical ranges by endpoints includeall numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2,2.75, 3, 3.80, 4, 5, etc.).

Furthermore, disclosure of a range includes disclosure of all subrangesincluded within the broader range (e.g., 1 to 5 discloses 1 to 4, 1.5 to4.5, 4 to 5, etc.).

Various embodiments of the invention have been described. These andother embodiments are within the scope of the following claims.

What is claimed is:
 1. A pharmaceutical composition comprising activeingredients, wherein the active ingredients of the pharmaceuticalcomposition are prepared from raw medicinal materials consisting of20-50 parts by weight of Epimedii Folium and 15-55 parts by weight ofPoria or Poria cum Radix Pini.
 2. A pharmaceutical compositioncomprising active ingredients, wherein the active ingredients of thepharmaceutical composition are prepared from raw medicinal materialsconsisting of 20-50 parts by weight of Epimedii Folium, 15-55 parts byweight of Poria or Poria cum Radix Pini and 10-55 parts by weight ofAcanthopanax.
 3. The pharmaceutical composition as claimed in claim 2,wherein the active ingredients of the pharmaceutical composition areprepared from raw medicinal materials consisting of 20-30 parts byweight of Epimedii Folium, 20-45 parts by weight of Poria or Poria cumRadix Pini and 20-55 parts by weight of Acanthopanax.
 4. Thepharmaceutical composition as claimed in claim 3, wherein the activeingredients of the pharmaceutical composition are prepared from rawmedicinal materials consisting of 30 parts by weight of Epimedii Folium,30 parts by weight of Poria or Poria cum Radix Pini, and 35 parts byweight of Acanthopanax.
 5. A pharmaceutical composition comprisingactive ingredients, wherein the active ingredients of the pharmaceuticalcomposition are prepared from raw medicinal materials consisting of20-50 parts by weight of Epimedii Folium, 15-50 parts by weight of Poriaor Poria cum Radix Pini, 15-50 parts by weight of Acanthopanax and 6-15parts by weight of Anemarrhenae Rhizoma.
 6. The pharmaceuticalcomposition as claimed in claim 5, wherein the active ingredients of thepharmaceutical composition are prepared from raw medicinal materialsconsisting of 20-30 parts by weight of Epimedii Folium, 20-30 parts byweight of Poria or Poria cum Radix Pini, 25-50 parts by weight ofAcanthopanax, and 10-15 parts by weight of Anemarrhenae Rhizoma.
 7. Thepharmaceutical composition as claimed in claim 6, wherein the activeingredients of the pharmaceutical composition are prepared from rawmedicinal materials consisting of 30 parts by weight of Epimedii Folium,30 parts by weight of Poria or Poria cum Radix Pini, 25 parts by weightof Acanthopanax and 15 parts by weight of Anemarrhenae Rhizoma.
 8. Thepharmaceutical composition as claimed in claim 1, wherein said Poria isprocessed by: extracting said weight parts of Poria with water 2-3 timeseach for 1-3 hours, to generate a resulting extract solution, wherein afirst extraction of Poria is carried out with water that is 6-10 timesthe weight of Poria, and a second extraction of Poria is carried outwith water that is 4-8 times the weight of Poria; and filtering theresulting extract solution and concentrating the resulting extractsolution into a dry extract under reduced pressure.
 9. Thepharmaceutical composition as claimed in claim 1, wherein said EpimediiFolium is processed by: extracting said weight parts of Epimedii Foliumwith 30-70% ethanol solution 2-3 times each for 1-3 hours, to produce aresulting extract solution, wherein a first extraction of EpimediiFolium is carried out with 30-70% ethanol solution that is 7-16 timesthe weight of Epimedii Folium, and a second extraction of EpimediiFolium is carried out with 30-70% ethanol solution that is 4-12 timesthe weight of Epimedii Folium; and filtering the resulting extractsolution and recovering ethanol under reduced pressure followed byconcentrating the resulting extract solution into a dry extract.
 10. Thepharmaceutical composition as claimed in claim 2, wherein saidAcanthopanax is processed by: extracting said weight parts ofAcanthopanax with water 2-3 times each for 1-3 hours, to generate aresulting extract solution, wherein a first extraction of Acanthopanaxis carried out with water that is 6-10 times the weight of Acanthopanax,and a second extraction of Acanthopanax is carried out with water thatis 4-8 times the weight of Acanthopanax; and filtering the resultingextract solution and concentrating the resulting extract solution into adry extract under reduced pressure.
 11. The pharmaceutical compositionas claimed in claim 5, wherein said Anemarrhenae Rhizoma is processedby: placing said weight parts of Anemarrhenae Rhizoma into water that is6-10 times the weight of Anemarrhenae Rhizoma, heating the water untilthe water and Anemarrhenae Rhizoma boils and then decocting AnemarrhenaeRhizoma for 2-4 hours, removing and keeping the supernatant liquid,repeating the heating and removing on the resulting residue again togenerate a combined extract solution, and then filtering the combinedextract solution followed by concentrating the combined extract solutioninto a dry extract.